负载超顺磁性氧化铁纳米颗粒的人 T 细胞保持抗原特异性 TCR 功能。

BACKGROUND: Immunotherapy of cancer is an emerging field with the potential to improve long-term survival. Thus far, adoptive transfer of tumor-specific T cells represents an effective treatment option for tumors of the hematological system such as lymphoma, leukemia or myeloma. However, in solid tumors, treatment efficacy is low owing to the immunosuppressive microenvironment, on-target/off-tumor toxicity, limited extravasation out of the blood vessel, or ineffective trafficking of T cells into the tumor region. Superparamagnetic iron oxide nanoparticles (SPIONs) can make cells magnetically controllable for the site-specific enrichment. METHODS: In this study, we investigated the influence of SPION-loading on primary human T cells for the magnetically targeted adoptive T cell therapy. For this, we analyzed cellular mechanics and the T cell response after stimulation via an exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65 and compared them to T cells that had not received SPIONs. RESULTS: SPION-loading of human T cells showed no influence on cellular mechanics, therefore retaining their ability to deform to external pressure. Additionally, SPION-loading did not impair the T cell proliferation, expression of activation markers, cytokine secretion, and tumor cell killing after antigen-specific activation mediated by the TCR. CONCLUSION: In summary, we demonstrated that SPION-loading of T cells did not affect cellular mechanics or the functionality of the endogenous or an exogenous TCR, which allows future approaches using SPIONs for the magnetically enrichment of T cells in solid tumors.

背景：癌症的免疫疗法是一个新兴领域，具有提高长期生存率的潜力。到目前为止，肿瘤特异性 T 细胞的过继转移代表了一种针对血液系统肿瘤（如淋巴瘤、白血病或骨髓瘤）的有效治疗选择。然而，在实体肿瘤中，由于免疫抑制微环境、针对目标/脱靶毒性、有限的血管外渗或 T 细胞向肿瘤区域的有效转运，治疗效果较低。超顺磁氧化铁纳米颗粒（SPIONs）可使细胞具有磁性可控性，从而实现特异性富集。

方法：在这项研究中，我们研究了 SPION 加载对原代人 T 细胞用于磁性靶向过继 T 细胞治疗的影响。为此，我们分析了细胞力学和刺激后 T 细胞的反应，这些刺激通过针对黑色素瘤抗原 MelanA 的外源性 T 细胞受体（TCR）或针对巨细胞病毒抗原 pp65 的内源性 TCR 进行特异性刺激，并将其与未接受 SPION 的 T 细胞进行比较。

结果：SPION 加载对人 T 细胞的细胞力学没有影响，因此保留了它们对外界压力变形的能力。此外，SPION 加载不会损害 T 细胞增殖、激活标志物表达、细胞因子分泌和抗原特异性激活介导的肿瘤细胞杀伤作用。

结论：总之，我们证明了 T 细胞的 SPION 加载不会影响细胞力学或内源性或外源性 TCR 的功能，这允许未来使用 SPION 来磁性富集实体瘤中的 T 细胞。